{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(10)"],"submitter":["Mizojiri R"],"pubmed_abstract":["Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized, and evaluated for identification of orally bioavailable probe molecules. Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord with their promising PK profiles and results from initial in vivo PD studies, compounds 1o and 1q showed antitumor efficacy with T/C values of 54% and 29%, respectively, without severe body weight loss. Thus, our novel series of compounds represents promising probe molecules for the in vivo pharmacological study of selective eIF4A3 inhibition."],"journal":["ACS medicinal chemistry letters"],"pagination":["1077-1082"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5642020"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors."],"pmcid":["PMC5642020"],"pubmed_authors":["Fukuda K","Nakata D","Kosaka M","Iwatani-Yoshihara M","Sasaki S","Kosugi Y","Cary DR","Mizojiri R","Shibata S","Arai R","Morishita D","Takami K","Kamaura M","Satoh Y","Takeda J","Imaeda Y"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as Orally eIF4A3-Selective Inhibitors.","description":"Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized, and evaluated for identification of orally bioavailable probe molecules. Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord with their promising PK profiles and results from initial in vivo PD studies, compounds 1o and 1q showed antitumor efficacy with T/C values of 54% and 29%, respectively, without severe body weight loss. Thus, our novel series of compounds represents promising probe molecules for the in vivo pharmacological study of selective eIF4A3 inhibition.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Oct","modification":"2025-05-29T19:15:13.805Z","creation":"2025-05-29T19:15:13.805Z"},"accession":"S-EPMC5642020","cross_references":{"pubmed":["29057054"],"doi":["10.1021/acsmedchemlett.7b00283"]}}